Precision, Functional Glyconanoassemblies through Supramolecular Design

University Of California, San Diego, La Jolla CA

Investigators

Abstract

PROJECT SUMMARY Carbohydrates present an important class among the natural building blocks of biopolymers as glycan-protein interactions participate in many essential biological processes including immune function, cell-signaling, the recognition of pathogens, among others. Understanding the nature of these interactions has sparked a growing interest in building synthetic glycan assemblies that can probe and mimic these natural recognition events and inform the design of effective antiviral and therapeutic agents. Despite ongoing interest, however, existing glycoassembly platforms such as dendrimers, nanoparticles, and polymers often face fundamental limitations including non-uniform composition and size, lack of atomic precision, and limited architectural tunability. These challenges hinder precise control over their molecular recognition behavior and limit our understanding of the structure-activity paradigms essential to their function. The proposed research seeks to address these limitations by employing a coordination-driven self-assembly approach of synthesizing multivalent glycomolecules with atomic precision. This new supramolecular synthetic strategy advances the state-of-the-art abiotic systems by introducing a modular and programmable method of designing key structural parameters including architectural size, shape, charge, rigidity, and morphology, which are essential factors for probing and understanding structure-activity relationships involved in biomacromolecular recognition. By employing a platform that offers the topological surface density and complexity characteristic of nanoparticles with the synthetic control afforded by small molecule systems, the proposed work aims to provide the ability to optimize glyconanoassemblies for enhanced protein recognition and selectivity. Through this unique synthetic approach, we aim to establish a new paradigm for studying glycan-protein recognition that provides fundamental insights into the design of therapeutic strategies to treat conditions where multivalent interactions play a pivotal role. Because our work is positioned at the interface of molecular synthesis, inorganic chemistry, chemical biology and materials science, we are equipped with a vast array of tools to advance and develop this interdisciplinary program.